Abstract
(S)-Bromohomoibotenic acid [(S)-BrHIbo] stereoselectively antagonized glutamate-stimulated phosphoinositide (PI) hydrolysis in baby hamster kidney (BHK) cells expressing mGluR1a in a competitive manner with an IC50 of 250 microM. However, (S)-BrHIbo did not inhibit (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced PI hydrolysis in rat hippocampal slices (S)- or (R)-BrHIbo did not show any effects on forskolin-stimulated cAMP-formation in BHK cells expressing mGluR2 or mGluR4 but did displace [3H]2-amino-4-phosphonobutyrate ([3H]AP4) binding from rat corticalmembranes with high affinities (IC50 = 1.0 microM and 1.1 microM, respectively). These data suggest that (S)-BrHIbo may interest with multiple PI-coupled glutamate receptors, however, at concentrations that are several fold higher than for displacement of [3H]AP4 binding from rat cortical membranes.
MeSH terms
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Aminobutyrates / metabolism
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Animals
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Binding, Competitive
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Cell Line
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Cerebral Cortex / metabolism
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Cricetinae
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Cyclic AMP / metabolism
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Cycloleucine / analogs & derivatives
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Cycloleucine / pharmacology
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Dose-Response Relationship, Drug
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Glutamic Acid / metabolism
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Glutamic Acid / pharmacology
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Hippocampus / metabolism
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Hydrolysis / drug effects
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Ibotenic Acid / analogs & derivatives*
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Ibotenic Acid / chemistry
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Ibotenic Acid / metabolism
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Ibotenic Acid / pharmacology
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Kidney / cytology
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Kidney / metabolism*
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Membranes / metabolism
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Phosphatidylinositols / metabolism
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Quinoxalines / pharmacology
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Receptors, AMPA / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / classification
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Receptors, Metabotropic Glutamate / drug effects*
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Receptors, Metabotropic Glutamate / metabolism*
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Stereoisomerism
Substances
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Aminobutyrates
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Phosphatidylinositols
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Quinoxalines
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Receptors, AMPA
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Receptors, Metabotropic Glutamate
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Cycloleucine
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1-amino-1,3-dicarboxycyclopentane
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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4-bromohomoibotenic acid
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Ibotenic Acid
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Glutamic Acid
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Cyclic AMP
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2-amino-4-phosphonobutyric acid